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Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in Bos indicus (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus. Five transcription factors (TF) with potential regulatory roles in the hypothalamus were identified in this experiment: E2F8, NFAT5, SIX5, ZBTB38, and ZNF605. These TF genes were significantly differentially expressed in the hypothalamus of postpubertal versus prepubertal heifers and were also identified as significant according to the applied regulatory impact factor metric (P < 0.05). Two of these 5 TF, ZBTB38 and ZNF605, were zinc fingers, belonging to a gene family previously reported to have a central regulatory role in mammalian puberty. The SIX5 gene belongs to the family of homologues of Drosophila sine oculis (SIX) genes implicated in transcriptional regulation of gonadotrope gene expression. Tumor-related genes such as E2F8 and NFAT5 are known to affect basic cellular processes that are relevant in both cancer and developmental processes. Mutations in NFAT5 were associated with puberty in humans. Mutations in these TF, together with other genetic determinants previously discovered, could be used in genomic selection to predict the genetic merit of cattle (i.e., the likelihood of the offspring presenting earlier than average puberty for Brahman). Knowledge of key mutations involved in genetic traits is an advantage for genomic prediction because it can increase its accuracy. [ABSTRACT FROM AUTHOR]

Harsh tropical environments impose serious challenges on poorly adapted species. In beef cattle, tropical adaptation in the form of temperature and disease resistance, coupled with acclimatization to seasonal and limited forage, comes at a cost to production efficiency. Prominent among these costs is delayed onset of puberty, a challenging phenotype to manipulate through traditional breeding mechanisms. Recently, system biology approaches, including gene networks, have been applied to the genetic dissection of complex phenotypes. We aimed at developing and studying gene networks underlying cattle puberty. Our starting material comprises the association results of ~50,000 SNP on 22 traits, including age at puberty, and 2 cattle breed populations: Brahman (n = 843) and Tropical Composite (n = 866). We defined age at puberty as the age at first corpus luteum (AGECL). By capturing the genes harboring mutations minimally associated (P < 0.05) to AGECL or to a set of traits related with AGECL, we derived a gene network for each breed separately and a third network for the combined data set. At the intersection of the 3 networks, we identified candidate genes and pathways that were common to both breeds. Resulting from these analyses, we identified an enrichment of genes involved in axon guidance, cell adhesion, ErbB signaling, and glutamate activity, pathways that are known to affect pulsatile release of GnRH, which is necessary for the onset of puberty. Furthermore, we employed network connectivity and centrality parameters along with a regulatory impact factor metric to identify the key transcription factors (TF) responsible for the molecular regulation of puberty. As a novel finding, we report 5 TF (HIVEP3, TOX, EYA1, NCOA2, and ZFHX4) located in the network intersecting both breeds and interacting with other TF, forming a regulatory network that harmonizes with the recent literature of puberty. Finally, we support our network predictions with evidence derived from gene expression in hypothalamic tissue of adult cows. [ABSTRACT FROM AUTHOR]